Exudative diathesis produced by vitamin e-deficient diets without polyenoic fatty acids

Zusammenfassung Bei Fütterung von Küken mit einer Vitamin-E-freien Nahrung, die als Eiweissquelle eine spezielle Trockenhefe, frei von mehrfach ungesättigten Fettsäuren, enthielt, wurde eine jedoch verhältnismässig milde, exsudative Diathese beobachtet.     

Dialogue and Revolution: Proposal for Critical-Pragmatic Recursive Praxis to Support Operationalisation of Methodological Virtues

Systemic Practice and Action Research (SPAR) denotes a family of approaches with different theoretical foundations, the constructive encounter between which may propel the movement forward. A persistent scholarly debate persists between the so-called emancipatory and pragmatic strands, motivating perceptions of the impossibility to jointly accomplish both ‘dialogical’ and ‘revolutionary’ commitments of the movement. This reflects that SPAR is still grappling with how to maintain a normative foundation while prioritising local change processes, thus reconciling what is universally ‘right’ with the locally ‘good’ in order to foster an operational view of the nature of reciprocity and justification. In this paper, I mobilise experiences from five action research projects in the field of natural resource governance to undertake a methodological introspection to examine how we as SPAR professionals may negotiate our approach during project implementation and the encounter of concrete realities and stakeholder interests. The objective is to offer an alternative view on the relationship between the ‘dialogical’ and the ‘revolutionary’ elements of SPAR; a view which rejects a dichotomisation in favour of a critical-pragmatic recursive praxis that depends on the capacity of the researcher to negotiate methodological virtues with co-researchers in the process.     

The genome sequence of Atlantic cod reveals a unique immune system

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.     

Structure and function of an irreversible agonist-β(2) adrenoceptor complex

G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs, the molecular basis for agonist binding and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered by modest affinities and rapid off-rates of available agonists. Using the inactive structure of the human β(2) adrenergic receptor (β(2)AR) as a guide, we designed a β(2)AR agonist that can be covalently tethered to a specific site on the receptor through a disulphide bond. The covalent β(2)AR-agonist complex forms efficiently, and is capable of activating a heterotrimeric G protein. We crystallized a covalent agonist-bound β(2)AR-T4L fusion protein in lipid bilayers through the use of the lipidic mesophase method, and determined its structure at 3.5?? resolution. A comparison to the inactive structure and an antibody-stabilized active structure (companion paper) shows how binding events at both the extracellular and intracellular surfaces are required to stabilize an active conformation of the receptor. The structures are in agreement with long-timescale (up to 30?μs) molecular dynamics simulations showing that an agonist-bound active conformation spontaneously relaxes to an inactive-like conformation in the absence of a G protein or stabilizing antibody.     

Non-canonical inflammasome activation targets caspase-11

Caspase-1 activation by inflammasome scaffolds comprised of intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and the adaptor ASC is believed to be essential for production of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 during the innate immune response. Here we show, with C57BL/6 Casp11 gene-targeted mice, that caspase-11 (also known as caspase-4) is critical for caspase-1 activation and IL-1β production in macrophages infected with Escherichia coli, Citrobacter rodentium or Vibrio cholerae. Strain 129 mice, like Casp11(-/-) mice, exhibited defects in IL-1β production and harboured a mutation in the Casp11 locus that attenuated caspase-11 expression. This finding is important because published targeting of the Casp1 gene was done using strain 129 embryonic stem cells. Casp1 and Casp11 are too close in the genome to be segregated by recombination; consequently, the published Casp1(-/-) mice lack both caspase-11 and caspase-1. Interestingly, Casp11(-/-) macrophages secreted IL-1β normally in response to ATP and monosodium urate, indicating that caspase-11 is engaged by a non-canonical inflammasome. Casp1(-/-)Casp11(129mt/129mt) macrophages expressing caspase-11 from a C57BL/6 bacterial artificial chromosome transgene failed to secrete IL-1β regardless of stimulus, confirming an essential role for caspase-1 in IL-1β production. Caspase-11 rather than caspase-1, however, was required for non-canonical inflammasome-triggered macrophage cell death, indicating that caspase-11 orchestrates both caspase-1-dependent and -independent outputs. Caspase-1 activation by non-canonical stimuli required NLRP3 and ASC, but caspase-11 processing and cell death did not, implying that there is a distinct activator of caspase-11. Lastly, loss of caspase-11 rather than caspase-1 protected mice from a lethal dose of lipopolysaccharide. These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections.     

Fast core rotation in red-giant stars as revealed by gravity-dominated mixed modes

When the core hydrogen is exhausted during stellar evolution, the central region of a star contracts and the outer envelope expands and cools, giving rise to a red giant. Convection takes place over much of the star's radius. Conservation of angular momentum requires that the cores of these stars rotate faster than their envelopes; indirect evidence supports this. Information about the angular-momentum distribution is inaccessible to direct observations, but it can be extracted from the effect of rotation on oscillation modes that probe the stellar interior. Here we report an increasing rotation rate from the surface of the star to the stellar core in the interiors of red giants, obtained using the rotational frequency splitting of recently detected 'mixed modes'. By comparison with theoretical stellar models, we conclude that the core must rotate at least ten times faster than the surface. This observational result confirms the theoretical prediction of a steep gradient in the rotation profile towards the deep stellar interior.     

The exudative diathesis produced by torula yeast

Zusammenfassung Die exsudative Diathese, welche bei Küken durch Verfütterung einer Vitamin-E-freien Nahrung mit Torulahefe als Proteinquelle hervorgerufen wird, wird mit dem nicht unbeträchtlichen Gehalt dieser Hefe an leicht oxydierbaren Fettsäuren in Verbindung gesetzt.Die Vitamin-E-freie Torula-Hefe-Nahrung führt zu Peroxydation des Körperfettes, wie es früher in entsprechenden Versuchen mit Kasein-Lebertran-Nahrungen gefunden wurde.Die von amerikanischen Forschern gefundene Schutzwirkung von Selen gegen exsudative Diathese wird bestätigt.Das Auftreten von Encephalomalacie wurde durch Selen nicht verhindert.

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We are grateful to Lake States Yeast Corporation, Rhinelander, Wisconsin, for supply of the torula yeast used in these experiments.     

The impact of specialized enemies on the dimensionality of host dynamics

Although individual species persist within a web of interactions with other species, data are usually gathered only from the focal species itself. We ask whether evidence of a species' interactions be detected and understood from patterns in the dynamics of that species alone. Theory predicts that strong coupling between a prey and a specialist predator/parasite should lead to an increase in the dimensionality of the prey's dynamics, whereas weak coupling should not. Here we describe a rare test of this prediction. Two natural enemies were added separately to replicate populations of a moth. For biological reasons that we identify here, the prediction of increased dimensionality was confirmed when a parasitoid wasp was added (although this increase had subtleties not previously appreciated), but the prediction failed for an added virus. Thus, an imprint of the interactions may be discerned within time-series data from component species of a system.     

Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA

Repair of DNA damage is essential for maintaining genome integrity, and repair deficiencies in mammals are associated with cancer, neurological disease and developmental defects. Alkylation damage in DNA is repaired by at least three different mechanisms, including damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine by Escherichia coli AlkB. By contrast, little is known about consequences and cellular handling of alkylation damage to RNA. Here we show that two human AlkB homologues, hABH2 and hABH3, also are oxidative DNA demethylases and that AlkB and hABH3, but not hABH2, also repair RNA. Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. In addition, AlkB and hABH3 expressed in E. coli reactivate methylated RNA bacteriophage MS2 in vivo, illustrating the biological relevance of this repair activity and establishing RNA repair as a potentially important defence mechanism in living cells. The different catalytic properties and the different subnuclear localization patterns shown by the human homologues indicate that hABH2 and hABH3 have distinct roles in the cellular response to alkylation damage.